Abstract

Dyotropic rearrangements of fused, tricyclic ?-lactones are described that proceed via unprecedented stereospecific, 1,2-acyl migrations delivering bridged, spiro-?-butyrolactones. A unique example of this dyotropic process involves a fused bis-lactone possessing both ?- and ?-lactone moieties which enabled rapid access to the core structures of curcumanolide A and curcumalactone. Our current mechanistic understanding of the latter dyotropic process, based on computational studies, is also described. Other key transformations in the described divergent syntheses of (-)-curcumanolide A and (-)-curcumalactone from a common intermediate (11 and 12 steps from 2-methyl-1,3-cyclopentanedione, respectively), include a catalytic, asymmetric nucleophile (Lewis base)-catalyzed aldol-lactonization (NCAL) leading to a tricyclic ?-lactone, a Baeyer-Villiger oxidation in the presence of a ?-lactone, and highly facial-selective and stereocomplementary reductions of an intermediate spirocyclic enoate. The described dyotropic rearrangements significantly alter the topology of the starting tricyclic ?-lactone, providing access to complex spirocyclic cyclopentyl-?-lactones and bis-?-lactones in a single synthetic operation.